Outcome of second conditioned allogeneic stem cell transplant in children with non-SCID inborn errors of immunity

Graft failure (GF) after allogeneic hematopoietic stem cell transplant (HSCT) is a life-threatening complication. The Inborn Errors Working Party conducted a retrospective study to examine the outcome of a second HSCT for children with nonsevere combined immunodeficiency (SCID) inborn errors of immunity (IEI); 159 children from 37 centers who received a second transplant between 2009 and 2020 were included in this analysis. The median interval between first and second HSCT was 6.9 months (0.7-155.2 months). The 5-year overall survival (OS) and event-free survival (EFS) rates were 78% and 69%, respectively. The second HSCT for primary GF had a significantly lower OS (69%, 55%-83% vs secondary GF, 81%, 73%-89%; P = .044) and EFS (52%, 37%-68% vs secondary GF, 75%, 67%-84%; P< .001). Improved EFS was observed in patients who received myeloablative conditioning/reduced-toxicity conditioning (74%, 66%-81%) compared with nonmyeloablative conditioning (50%, 29%-71%; P = .003), but this association was not observed in OS. Upon multivariable analysis, cord blood was the only independent negative predictor for EFS (hazard ratio, 4.9, 1.3-18.7; P = .020). The 1-year cumulative incidence (CIN) of all GF after the second HSCT was 13% (95% confidence interval, 8%-19%). The day-100 CINs of grade 2 and grade 3 to 4 acute graft-versus-host disease were 19% (13%-25%) and 8% (4%-13%), respectively. Whole-blood chimerism >90% was reported in 84.3% at last follow-up. We report, to our knowledge, the first international experience with the largest cohort of second conditioned HSCT in non-SCID IEI to date. This study provides valuable insights into the clinical outcomes following second transplant, identifying key predictors of survival.